JP2004175786A - Composition for treating i-type allergic disorder - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a medicinal composition effective for treating I-type allergic disorders while maintaining suppressive action of ketotifen on sternutation and nasal hypersecretion and increasing suppressive action on nasal congestion. <P>SOLUTION: This composition for treating I-type allergic disorders contains ketotifen and pseudoephedorine. <P>COPYRIGHT: (C)2004,JPO

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a pharmaceutical composition effective for type I allergic diseases such as allergic rhinitis, and more specifically, a composition for treating type I allergic disease containing ketotifen and pseudoephedrine and having an enhanced inhibitory effect on nasal congestion symptoms. About.
[0002]
[Prior art]
It is known that type I allergic diseases such as allergic rhinitis show a biphasic reaction of an immediate phase reaction and a delayed phase reaction. The immediate phase reaction in this type I allergic disease is characterized in that an allergic reaction such as sneezing, runny nose, nasal congestion, etc. is induced immediately after contact with an antigen (allergen) such as pollen. On the other hand, the late-phase reaction is characterized by re-emerging allergic reactions such as nasal congestion several hours after antigen sensitization.
[0003]
Conventionally, ketotifen has been administered as an anti-allergic drug with an antihistamine action as the main effect in the treatment of allergic rhinitis, but sneezing in the immediate phase reaction and a strong inhibitory effect on runny nose, but nasal congestion symptoms Was not sufficient.
[0004]
[Problems to be solved by the invention]
Therefore, an object of the present invention is to provide a pharmaceutical composition which is effective in treating type I allergic disease by enhancing the nasal congestion inhibitory effect while maintaining the inhibitory effect of ketotifen on sneezing and runny nose.
[0005]
[Means for Solving the Problems]
The present inventors have conducted intensive studies to solve the above-described problems, and found that a composition comprising ketotifen and pseudoephedrine known as a sympathomimetic has an effect of reducing nasal congestion caused by type I allergic disease. And completed the present invention.
[0006]
That is, one aspect of the present invention is a composition for treating type I allergic disease, comprising ketotifen and pseudoephedrine.
[0007]
Another embodiment of the present invention is a composition for treating allergic rhinitis, which comprises ketotifen and pseudoephedrine.
[0008]
Still another embodiment of the present invention is a composition for improving nasal congestion symptoms, which comprises ketotifen and pseudoephedrine.
[0009]
The “ketotifen” used in the present invention is an antiallergic drug having an antihistamine action, which may be a salt. Particularly preferred is ketotifen fumarate.
[0010]
"Pseudoephedrine" used in the present invention is a sympathomimetics. Here, the sympathetic stimulant refers to a drug that exhibits the same effect as when stimulating an adrenergic nerve, and is also called an adrenergic agonist. Pseudoephedrine may be a salt.
[0011]
BEST MODE FOR CARRYING OUT THE INVENTION
The effective amount of "ketotifen" in the present invention is 0.1 to 10 mg per day for an adult in the case of oral administration.
[0012]
In the present invention, the effective amount of "pseudoephedrine" in the case of oral administration is 5 to 300 mg, preferably 10 to 240 mg per day for an adult.
[0013]
The composition according to the present invention is prepared into an oral administration preparation, and is provided, for example, as a solid preparation such as tablets, pills, capsules, powders, granules and chewables, or as a liquid preparation such as syrups and drinks. It can be administered once or several times a day.
[0014]
When prepared as a solid preparation, excipients, lubricants, disintegrants and the like can be used as necessary. When prepared as a liquid preparation, a surfactant, a solubilizing agent, if necessary, can be used. Agents, buffers and the like can be used.
[0015]
Further, preservatives, flavors, pigments, sweeteners, flavoring agents, cooling agents, and the like may be added.
[0016]
【Example】
Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples.
[0017]
(Example 1)
Ketotifen fumarate 2g
140g of pseudoephedrine
Belladonna Total Alkaloid 0.4g
100g anhydrous caffeine
Mannit 900g
980g corn starch
180 g of hydroxypropyl cellulose
After the above components were weighed, uniformly mixed and pulverized, 200 g of ethanol was added and kneaded. After extrusion granulation, it was dried to produce columnar granules. This was divided into 1200 mg per packet to obtain granules.
[0018]
(Example 2)
Ketotifen fumarate 2g
140g of pseudoephedrine
Belladonna Total Alkaloid 0.4g
100g anhydrous caffeine
900g crystalline cellulose
150 g of hydroxypropyl cellulose
Low-substituted hydroxypropylcellulose 400g
After the above components were weighed, uniformly mixed and pulverized, 140 g of ethanol was added to perform stirring granulation. After drying, 10 g of magnesium stearate was added and mixed, and the mixture was tableted to a tablet weight of 300 mg to obtain tablets.
[0019]
(Example 3)
Ketotifen fumarate 2g
140g of pseudoephedrine
Belladonna Total Alkaloid 0.4g
100g anhydrous caffeine
700g potato starch
Crystalline cellulose 120g
Hydroxypropyl cellulose 30g
Magnesium stearate 12g
After weighing the above components, uniformly mixing and pulverizing, dry granulation was performed. This was filled into No. 1 capsule so as to have a content of 300 mg to obtain a capsule.
[0020]
(Test example) [OVA-induced guinea pig nasal obstruction induction test]
[Experimental animals]
Hartrey guinea pigs (male, 4 weeks old) were used in the experiment.
[0021]
[Test drug]
Ketotifen and pseudoephedrine were used as test drugs.
[0022]
[Antigen sensitization]
Initial sensitization was performed by intraperitoneally administering 0.5 mL of a 2 mg / mL phosphate buffer (PBS) solution of ovalbumin (OVA) to a Hartrey guinea pig. Two days after the first sensitization, 0.5 mL of a 5 mg / mL PBS solution of OVA was intraperitoneally administered to perform resensitization.
[0023]
Twenty-three days after the first sensitization, a nasal congestion reaction was induced by instilling 40 μL of a 0.1% OVA PBS solution into both nasal passages of a guinea pig. After the induction, the nasal cavity resistance value for 0.75 hours was measured by a double flow plethysmograph method using an airway resistance measurement device (Muls, Inc., Pulmos I). The animals were divided into four groups.
[0024]
[Evaluation]
The test drugs ketotifen and pseudoephedrine were each dissolved in distilled water for injection and administered. The three groups, excluding the controls, are as follows.
[0025]
Administration group 1: pseudoephedrine 32 mg / kg
Administration group 2: Ketotifen 32 mg / kg
Administration group 3: pseudoephedrine and ketotifen 32 mg / kg each
[0026]
Each drug was administered intraperitoneally to guinea pigs grouped on day 28 of the first sensitization. In addition, distilled water for injection was similarly administered to the control group.
[0027]
One hour after administration of the drug, nasal congestion was induced by instilling 40 μL of a 0.2% OVA PBS solution into both nasal passages of the grouped guinea pigs. After the induction, the nasal cavity resistance value for 0.75 hours was measured by a double flow plethysmograph method using an airway resistance measurement device (Pulmos I, Inc., MIPS) to examine the effect of each drug on nasal congestion reaction.
[0028]
[Statistical processing and results]
The results are shown as mean ± se (FIG. 1). The test of the difference between the mean values of the multiple groups was performed using Dunnett's multiple comparison test.
[0029]
As a result, no inhibition was shown in the administration groups 1 and 2, but significant and synergistic inhibition was confirmed in the administration group 3 according to the present invention.
[0030]
Therefore, it has been clarified that even when the dose of ketotifen and pseudoephedrine alone does not show an effect, the combined use of ketotifen and pseudoephedrine can effectively suppress nasal congestion symptoms in allergic rhinitis.
[0031]
【The invention's effect】
According to the present invention, it has become possible to provide a pharmaceutical composition for effectively suppressing rhinitis symptoms, particularly nasal congestion, in allergic rhinitis.
[0032]
[Brief description of the drawings]
FIG. 1 is a graph showing nasal resistance values of a control group and drug administration groups 1 to 3.

Claims (3)

A composition for treating type I allergic disease, comprising ketotifen and pseudoephedrine. A composition for treating allergic rhinitis, comprising ketotifen and pseudoephedrine. A composition for improving nasal congestion, comprising ketotifen and pseudoephedrine.

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